全文获取类型
收费全文 | 100630篇 |
免费 | 7973篇 |
国内免费 | 3378篇 |
出版年
2023年 | 1541篇 |
2022年 | 1429篇 |
2021年 | 3178篇 |
2020年 | 3500篇 |
2019年 | 4677篇 |
2018年 | 4025篇 |
2017年 | 2879篇 |
2016年 | 2835篇 |
2015年 | 3610篇 |
2014年 | 6502篇 |
2013年 | 7806篇 |
2012年 | 4743篇 |
2011年 | 6139篇 |
2010年 | 4585篇 |
2009年 | 5234篇 |
2008年 | 5380篇 |
2007年 | 5354篇 |
2006年 | 4891篇 |
2005年 | 4249篇 |
2004年 | 3781篇 |
2003年 | 3023篇 |
2002年 | 2678篇 |
2001年 | 1801篇 |
2000年 | 1488篇 |
1999年 | 1299篇 |
1998年 | 1243篇 |
1997年 | 1012篇 |
1996年 | 990篇 |
1995年 | 1091篇 |
1994年 | 1019篇 |
1993年 | 836篇 |
1992年 | 864篇 |
1991年 | 727篇 |
1990年 | 655篇 |
1989年 | 558篇 |
1988年 | 489篇 |
1987年 | 465篇 |
1986年 | 383篇 |
1985年 | 545篇 |
1984年 | 717篇 |
1983年 | 470篇 |
1982年 | 580篇 |
1981年 | 459篇 |
1980年 | 373篇 |
1979年 | 368篇 |
1978年 | 286篇 |
1977年 | 253篇 |
1976年 | 220篇 |
1974年 | 143篇 |
1973年 | 181篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
《Current biology : CB》2020,30(24):4826-4836.e7
102.
Elevated PRC1 in gastric carcinoma exerts oncogenic function and is targeted by piperlongumine in a p53‐dependent manner 下载免费PDF全文
《Journal of cellular and molecular medicine》2017,21(7):1329-1341
Gastric carcinoma is one of the most common malignancies worldwide and the second most frequent cause of cancer‐related death in China. Protein regulator of cytokinesis 1 (PRC1) is involved in cytokinesis and plays key roles in microtubule organization in eukaryotes. This study was aimed to analyse the expression and to investigate the functional role of PRC1 in gastric tumorigenesis. The expression of PRC1 was evaluated by qRT‐PCR, Western blot and immunohistochemistry. The biological function of PRC1 was determined by CCK‐8 proliferation assays, monolayer colony formation, xenografted nude mice and cell invasion assays by shRNA‐mediated knockdown in AGS and HGC27 cells. The regulation of PRC1 expression by piperlongumine was also investigated using dual‐luciferase reporter assay and ChIP‐qPCR analysis. PRC1 was up‐regulated in primary gastric cancers. Overexpression of PRC1 in gastric cancers was associated with poor disease‐specific survival and overall survival. PRC1 knockdown in AGS and HGC27 cell lines suppressed proliferation, reduced monolayer colony formation, inhibited cell invasion and migration ability and induced cell‐cycle arrest and apoptosis. Inhibition of PRC1 also suppressed tumour growth in vivo. We finally confirmed that PRC1 is a novel downstream target of piperlongumine in gastric cancer. Our findings supported the oncogenic role of PRC1 in gastric carcinogenesis. PRC1 might serve as a prognostic biomarker and potential therapeutic target for gastric carcinoma. 相似文献
103.
《Animal : an international journal of animal bioscience》2017,11(5):811-819
Angiogenin is a member of the ribonuclease A superfamily of proteins that has been implicated in stimulating angiogenesis but whether angiogenin can directly affect ovarian granulosa or theca cell function is unknown. Therefore, the objective of these studies was to determine the effect of angiogenin on proliferation and steroidogenesis of bovine granulosa and theca cells. In experiments 1 and 2, granulosa cells from small (1 to 5 mm diameter) follicles and theca cells from large (8 to 22 mm diameter) follicles were cultured to evaluate the dose-response effect of recombinant human angiogenin on steroidogenesis. At 30 and 100 ng/ml, angiogenin inhibited (P<0.05) granulosa cell progesterone production and theca cell androstenedione production but did not affect (P>0.10) granulosa cell estradiol production or theca cell progesterone production, and did not affect numbers of granulosa or theca cells. In experiments 3 and 4, granulosa and theca cells from both small and large follicles were cultured with 300 ng/ml of angiogenin to determine if size of follicle influenced responses to angiogenin. At 300 ng/ml, angiogenin increased large follicle granulosa cell proliferation but decreased small follicle granulosa cell progesterone and estradiol production and large follicle theca cell progesterone production. In experiments 5 and 6, angiogenin stimulated (P<0.05) proliferation and DNA synthesis in large follicle granulosa cells. In experiment 7, 300 ng/ml of angiogenin increased (P<0.05) CYP19A1 messenger RNA (mRNA) abundance in granulosa cells but did not affect CYP11A1 mRNA abundance in granulosa or theca cells and did not affect CYP17A1 mRNA abundance in theca cells. We conclude that angiogenin appears to target both granulosa and theca cells in cattle, but additional research is needed to further understand the mechanism of action of angiogenin in granulosa and theca cells, as well as its precise role in folliculogenesis. 相似文献
104.
We have tested the effect of alkaloids (cocaine, morphine) and enkephalins on neutral endopeptidase of peripheral blood mononuclear cells activated by lectins. When treated with concanavalin A and cocaine, peripheral blood mononuclear cells showed an enhanced activity (+110 per cent) of the membrane neutral endopeptidase, which was not related to the expression of the common acute lymphoblastic leukemia antigen at the cell surface, although both molecules have the identical amino acid sequence. Phytohemagglutinin-P, morphine and synthetic enkephalins did not induce the activity of neutral endopeptidase nor the expression of common acute lymphoblastic leukemia antigen. Our findings suggested that the drugs of abuse, cocaine and morphine, affected specific membrane constituents without altering proliferation, subcellular localization of membrane enzymes or the surface immune phenotype of peripheral blood mononuclear cells. 相似文献
105.
Abstract SV1 was observed to have obvious synergism and could delay housefly ( Musca domestica vicina ) resistance development to Dipterex. The penetration rates of Dipterex through housefly cuticle were determined in a susceptible and two resistant strains. The results indicated that the penetration in the resistant housefly strains was obviously slower than in the susceptible one. The penetrating rate of SV1 + Dipterex (in mixture) was higher than that of Dipterex. The penetration reduction in resistant houseflies may be an important factor in bringing forth resistance. The increase of the penetrating rate of Dipterex and the decrease of its metabolic rate are regarded as the important mechanisms of SV1 synergism to Dipterex. 相似文献
106.
107.
Behnaz Valipour Kobra Velaei Ali Abedelahi Mohammad Karimipour Masoud Darabi Hojjatollah Nozad Charoudeh 《Journal of cellular physiology》2019,234(11):19352-19365
Natural killer (NK) cells have significant capability in tumor immune-surveillance. The ability of lyse transformed cells immediately in an antigen-independent manner make them an attractive candidate for cancer cell therapy. Despite employment of NK cells in cancer immunotherapy, clinical trials are faced with serious limitations such as trouble with the penetration of NK cells in tumor sites, limited in vivo persistence, and tumor microenvironment interference. Taken together, the NK-cell cancer therapy is still infant scenario that has a long way to be translated in clinic. Current article first reviews characteristic features of NK lymphocytes. Then, it discusses about important disruptive barriers and motivator in the developmental stages of NK cells like as tumor microenvironment. Finally, some revolutionary approaches are highlighted utilizing of NK cells in cancer therapy. 相似文献
108.
109.
Arash Salmaninejad Saeed Farajzadeh Valilou Arezoo Gowhari Shabgah Saeed Aslani Malihe Alimardani Alireza Pasdar Amirhossein Sahebkar 《Journal of cellular physiology》2019,234(10):16824-16837
Over the course of past few years, cancer immunotherapy has been accompanied with promising results. However, preliminary investigations with respect to immunotherapy concentrated mostly on targeting the immune checkpoints, nowadays, emerge as the most efficient strategy to raise beneficial antitumor immune responses. Programmed cell death protein 1 (PD-1) plays an important role in subsiding immune responses and promoting self-tolerance through suppressing the activity of T cells and promoting differentiation of regulatory T cells. PD-1 is considered as an immune checkpoint and protects against autoimmune responses through both induction of apoptosis in antigen-specific T cells and inhibiting apoptosis in regulatory T cells. Several clinical trials exerting PD-1 monoclonal antibodies as well as other immune-checkpoint blockades have had prosperous outcomes and opened new horizons in tumor immunotherapy. Nonetheless, a bulk of patients have failed to respond to these newly emerging immune-based approach and the survival rate was not satisfying. Additional strategies, especially combination therapies, has been initiated and been further promising. Attempts to identify novel and well-suited predictive biomarkers are also sensed. In this review, the promotion of cancer immunotherapy targeting PD-1 immunoinhibitory pathway is discussed. 相似文献
110.
Rene Rodriguez-Gutierrez Jose Gerardo González Deven Parmar Farheen. Shaikh Pio Cruz-López 《Journal of lipid research》2022,63(7):100233
Saroglitazar, being a dual PPAR-α/γ agonist, has shown beneficial effect in diabetic dyslipidemia and hypertriglyceridemia. Fibrates are commonly used to treat severe hypertriglyceridemia. However, the effect of saroglitazar in patients with moderate to severe hypertriglyceridemia was not evaluated. We conducted a study to compare the efficacy and safety of saroglitazar (4 mg) with fenofibrate (160 mg) in patients with moderate to severe hypertriglyceridemia. This was a multicenter, randomized, double-blinded, double-dummy, active-control, and noninferiority trial in adult patients with fasting triglyceride (TG) levels of 500–1,500 mg/dl. The patients were randomized in a 1:1 ratio to receive daily dose of saroglitazar or fenofibrate for 12 weeks. The primary efficacy end point was the percent change in TG levels at week 12 relative to baseline. The study comprised of 41 patients in the saroglitazar group and 41 patients in the fenofibrate group. We found that the percent reduction from baseline in TG levels at week 12 was significantly higher in the saroglitazar group (least square mean = ?55.3%; SE = 4.9) compared with the fenofibrate group (least square mean = ?41.1%; SE = 4.9; P = 0.048). Overall, 37 treatment-emergent adverse events (AEs) were reported in 24 patients (saroglitazar: 13; fenofibrate: 11). No serious AEs were reported, and no patient discontinued the study because of AEs. We conclude that saroglitazar (4 mg) is noninferior to fenofibrate (160 mg) in reducing TG levels after 12 weeks of treatment, was safe, and well tolerated. 相似文献